Ascorbate function and metabolism in the human erythrocyte

Abstract

Ascorbic acid, or vitamin C, is an important antioxidant in plasma, where it consumes oxygen free radicals and helps to preserve alpha-tocopherol (vitamin E) in lipoproteins. Erythrocytes, as the most plentiful cell in blood, help to preserve ascorbate in the blood plasma. In contrast to nucleated cells, which avidly concentrate ascorbate, the erythrocyte ascorbate concentration is the same as that in plasma. Erythrocytes nonetheless have a high capacity to regenerate the vitamin from its two electron-oxidized form, dehydroascorbic acid (DHA). DHA is rapidly taken up by these cells on the abundant glucose transport protein, GLUT1. Intracellular DHA is rapidly reduced to ascorbate by GSH in a direct chemical reaction, although enzyme-dependent mechanisms involving both glutaredoxin and thioredoxin reductase have also been demonstrated. Ascorbate, which carries a negative charge at physiologic pH, enters and leaves the cells slowly. Nonetheless, this slow release of ascorbate from erythrocytes can preserve both the plasma concentration of the vitamin, and prevent oxidation of alpha-tocopherol in low-density lipoprotein. In addition, intracellular ascorbate can spare and possibly recycle alpha-tocopherol in the erythrocyte membrane. In turn, alpha-tocopherol protects the cell membrane from lipid peroxidation. The ability of erythrocytes to recycle ascorbate, coupled with the ability of ascorbate to protect alpha-tocopherol in the cell membrane and in lipoproteins, provides a potentially important mechanism for preventing lipid peroxidative damage in areas of inflammation in the vascular bed, such as those involved with atherosclerosis.